TY - JOUR
T1 - Genetic signatures of gene flow and malariadriven natural selection in Sub-Saharan populations of the “endemic burkitt lymphoma belt”
AU - Gouveia, Mateus H.
AU - Bergen, Andrew W.
AU - Borda, Victor
AU - Nunes, Kelly
AU - Leal, Thiago P.
AU - Ogwang, Martin D.
AU - Yeboah, Edward D.
AU - Mensah, James E.
AU - Kinyera, Tobias
AU - Otim, Isaac
AU - Nabalende, Hadijah
AU - Legason, Ismail D.
AU - Mpoloka, Sununguko Wata
AU - Mokone, Gaonyadiwe George
AU - Kerchan, Patrick
AU - Bhatia, Kishor
AU - Reynolds, Steven J.
AU - Birtwum, Richard B.
AU - Adjei, Andrew A.
AU - Tettey, Yao
AU - Tay, Evelyn
AU - Hoover, Robert
AU - Pfeiffer, Ruth M.
AU - Biggar, Robert J.
AU - Goedert, James J.
AU - Prokunina-Olsson, Ludmila
AU - Dean, Michael
AU - Yeager, Meredith
AU - Lima-Costa, M. Fernanda
AU - Hsing, Ann W.
AU - Tishkoff, Sarah A.
AU - Chanock, Stephen J.
AU - Tarazona-Santos, Eduardo
AU - Mbulaiteye, Sam M.
N1 - Funding Information:
The work was funded by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics, National Cancer Institute (NCI) (Contracts HHSN261201100063C and HHSN261201100007I), and the Intramural Research Program, National Institute of Allergy and Infectious Diseases (S.J.R.), National Institutes of Health, Department of Health and Human Services. M.H.G., E.T.-S., T.P.L. and M.F.L.-C. are supported by Brazilian National Research Council (CNPq) and Minas Gerais Research Agency (FAPEMIG). M.H.G. performed part of this study as CAPES-PDSE fellow (99999.007069/2015-04), V.B. is a PEC-PG fellow (88882.195664/2018-01) of CAPES and K.N. performed the initial part of this study as CAPES-PNPD fellow-Brazil (1645581) and the latter part as United States National Institutes of Health fellow (R01 GM075091). Bioinformatics support was provided by the Sagarana HPC cluster, CPAD-ICB-UFMG, Brazil. The work in the Tishkoff laboratory was funded by RO1 grants from the National Institutes of Health (1R01DK104339-0 and 1R01GM113657-01). The content of this manuscript does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government. The content of this publication is the sole responsibility of the authors. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
Publisher Copyright:
© 2019, Public Library of Science. All rights reserved.
PY - 2019/3
Y1 - 2019/3
N2 - Populations in sub-Saharan Africa have historically been exposed to intense selection from chronic infection with falciparum malaria. Interestingly, populations with the highest malaria intensity can be identified by the increased occurrence of endemic Burkitt Lymphoma (eBL), a pediatric cancer that affects populations with intense malaria exposure, in the so called “eBL belt” in sub-Saharan Africa. However, the effects of intense malaria exposure and subSaharan populations’ genetic histories remain poorly explored. To determine if historical migrations and intense malaria exposure have shaped the genetic composition of the eBL belt populations, we genotyped ~4.3 million SNPs in 1,708 individuals from Ghana and Northern Uganda, located on opposite sides of eBL belt and with ≥ 7 months/year of intense malaria exposure and published evidence of high incidence of BL. Among 35 Ghanaian tribes, we showed a predominantly West-Central African ancestry and genomic footprints of gene flow from Gambian and East African populations. In Uganda, the North West population showed a predominantly Nilotic ancestry, and the North Central population was a mixture of Nilotic and Southern Bantu ancestry, while the Southwest Ugandan population showed a predominant Southern Bantu ancestry. Our results support the hypothesis of diverse ancestral origins of the Ugandan, Kenyan and Tanzanian Great Lakes African populations, reflecting a confluence of Nilotic, Cushitic and Bantu migrations in the last 3000 years. Natural selection analyses suggest, for the first time, a strong positive selection signal in the ATP2B4 gene (rs10900588) in Northern Ugandan populations. These findings provide important baseline genomic data to facilitate disease association studies, including of eBL, in eBL belt populations.
AB - Populations in sub-Saharan Africa have historically been exposed to intense selection from chronic infection with falciparum malaria. Interestingly, populations with the highest malaria intensity can be identified by the increased occurrence of endemic Burkitt Lymphoma (eBL), a pediatric cancer that affects populations with intense malaria exposure, in the so called “eBL belt” in sub-Saharan Africa. However, the effects of intense malaria exposure and subSaharan populations’ genetic histories remain poorly explored. To determine if historical migrations and intense malaria exposure have shaped the genetic composition of the eBL belt populations, we genotyped ~4.3 million SNPs in 1,708 individuals from Ghana and Northern Uganda, located on opposite sides of eBL belt and with ≥ 7 months/year of intense malaria exposure and published evidence of high incidence of BL. Among 35 Ghanaian tribes, we showed a predominantly West-Central African ancestry and genomic footprints of gene flow from Gambian and East African populations. In Uganda, the North West population showed a predominantly Nilotic ancestry, and the North Central population was a mixture of Nilotic and Southern Bantu ancestry, while the Southwest Ugandan population showed a predominant Southern Bantu ancestry. Our results support the hypothesis of diverse ancestral origins of the Ugandan, Kenyan and Tanzanian Great Lakes African populations, reflecting a confluence of Nilotic, Cushitic and Bantu migrations in the last 3000 years. Natural selection analyses suggest, for the first time, a strong positive selection signal in the ATP2B4 gene (rs10900588) in Northern Ugandan populations. These findings provide important baseline genomic data to facilitate disease association studies, including of eBL, in eBL belt populations.
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U2 - 10.1371/journal.pgen.1008027
DO - 10.1371/journal.pgen.1008027
M3 - Article
C2 - 30849090
AN - SCOPUS:85063630027
SN - 1553-7390
VL - 15
JO - PLoS genetics
JF - PLoS genetics
IS - 3
M1 - e1008027
ER -